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‘Nice, friendly yeast’ prompts a new approach

Yeast is as common in the lab as it is in a bakery. It’s a very useful organism because it grows quickly, is easy to culture, and its genetics have been studied extensively. But its very simplicity means it is also has limits – and those limits prompted Broad core member Aviv Regev and her colleagues to think about developing another model for studying cell circuitry.

Regev’s work, which she outlined in a recent talk at the Functional Genomics Data Society in Boston, focuses in part on our cells’ ability to respond to changes.

Regev focused on two kinds of changes cells must contend with: environmental changes like an attack from a pathogen and developmental changes that take place as cells mature. Regev’s lab group often uses yeast as a model organism for studying cell circuitry. But Regev’s group wanted to apply what’s been learned from studying yeast cells to mammals.

“One of our ambitions was to try to take some of the approaches and ideas that have matured within the genomic research community studying yeast and apply them in mammals,” Regev said. “We wanted to set our ambitions at the right scale and we wanted to find a cell system in mammals that would be as close as possible to nice, friendly yeast.”

Regev’s group arrived upon dendritic cells (DC) – immune cells in mammals that help defend against outside invaders like viruses and bacteria. “They’re like sentinels,” Regev explained. “They know how to recognize broad pathogen classes like bacteria, fungi, and viruses and when they encounter these pathogens, they mount appropriate responses.” Launching the right attack against a pathogen enemy is critical – if the cells respond the wrong way, the results can be fatal to the host.

Regev and her colleagues Ido Amit and Nir Hacohen wanted to find out how dendritic cells “know” what pathogen they’ve encountered and how they go about launching the right counter-attack. To uncover this, they traced the pathway from sensor molecules that recognize an invader and initiate a signal leading to changes in the way genes are expressed, which leads to a cell’s appropriate response (like an inflammatory response to a bacterial infection). Regev explained that when it comes to changes in gene expression, very little was known about how this network of signals is rewired to elicit these specific responses. Her group was able to shed light on the inner workings of this circuitry.

In her talk, titled “Reconstructing regulatory circuits: lessons from immune cells,” Regev also focused on insights into cell development. She and her colleagues Ben Ebert and Noa Novershtern studied hematopoiesis – the development of different kinds of blood cells (red blood cells, T-cells, B-cells, and much more), all of which are derived from hematopoietic stem cells (HSCs). From a small pool of HSCs, about 200 billion blood cells are created every single day. “That number just blows me away every time,” Regev said.

In order for a specific blood cell to form, it has to receive many, many signals that direct it toward development. If you imagine blood cells are cars, all start out at the same location, but at each fork in the road, cells receive signals that tell them what direction to take. All begin at the same starting point, but end up in very different places. Cells receive their directions from transcription factors, proteins that turn on or off specific genes. Interestingly, this doesn’t mean that each transcription factor is unique to one of kind of blood cell – the body reuses these factors for different cells at different junctures.

This spring, Regev, who is also an assistant professor at MIT, received an Early Career Scientist award from the Howard Hughes Medical Institute. You can read more about her group’s work by visiting her lab page.